Cell junctions , cell adhesion and extra cellular matrix

Overview of cell-cell communication via junctions, cell adhesion and ECM

1. CELL JUNCTIONS , CELL ADHESION AND EXTRA-CELLULAR MATRIX By: Minali Singh

2. What are cell junctions? The cell junction is a cell-cell or cell-extracellular matrix contact within a tissue of a multi-cellular organism, especially abundant in epithelia in order to create pathways for communication, allowing cells to exchange the signals that co-ordinate their behavior and regulate their patterns of gene expression.

3. FOUR FUNCTIONAL CLASSES OF CELL JUNCTIONS ANCHORING JUNCTIONS - link cell to cell (via cadherins ) or cell to ECM (via trans-membrane integrins ). OCCLUDING JUNCTIONS - Seal the gaps between cells in epithelia to make cell sheet into a impermeable/ selectively permeable barrier. CHANNEL-FORMING JUNCTIONS - Link the cytoplasm of adjacent cells. SIGNAL-RELAYING JUNCTIONS - Involve anchorage proteins for cell to cell signal transduction. ANCHORING JUNCTIONS OCCLUDING JUNCTIONS CHANNEL-FORMING JUNCTIONS SIGNAL-RELAYING JUNCTIONS

4. CADHERINS Cadherins are named for  calcium dependent adhesion . The external domain of a cadherin molecule - is made up of many repeats of the same protein chain. Each repeat has a space for binding calcium. Calcium makes the chain rigid, helping it to connect with a chain from another cell. In addition to an extracellular (outside the cell) component, cadherins also have a piece that penetrates through the membrane and a piece that is inside the cell. The interior portions of the cadherins form a complex within the cell. Figure : Cells of early embryo at about 8-celled stage begin to express E- Cadherin and as a result become strongly adherent to one another.

5. CLASSES OF CADHERINS Classical cadherins  include E- cadherin , P- cadherin and N- cadherin .They all have a similar structure, with five extracellular cadherin repeats, a transmembrane domain, and an intracellular domain. Adhesion by classic cadherins is involved in some significant cellular signaling pathways, including Wnt , Hedgehog, Ras , and RhoGTPase signaling . D esmosomal cadherins includes Desmoglein and desmocollin . They are important in forming a type of cellular junction called a desmosome . Protocadherins   are a large group of cadherin molecules present in a wide range of species that are thought to be related to an ancestral cadherin . Their extracellular domains have more than five repeated cadherin motifs, distinguishing them from classical cadherins . The intracellular domains of the proto- cadherins are also different from their classical cousins. They are highly variable, with a variety of functions in the nervous system, including neuronal differentiation and the formation of synapses. Unconventional cadherins  are a large group of cadherins that are not otherwise categorized into the previous three groups. They include VE- cadherin , R- cadherin , and many others.

6. SELECTIVE CELL-CELL ADHESIO N Cadherins mediate highly selective recognition, enabling cells of similar type to stick together and stay segregated from other types of cells. Epidermal cell Mesodermal cell Neural-plate cell

7. ADHERENS JUNCTIONS Adherens junctions are cell-cell adhesion complexes that are continuously assembled and disassembled, allowing cells within a tissue to respond to forces, biochemical signals and structural changes in their microenvironment. The events leading up to  adherens junction formation are still not entirely clear, but they ultimately result in the recruitment of transmembrane   cadherins , catenins  ( beta- catenins ,  alpha- catenins )and cytoskeletal adaptor proteins that form the primary architecture of adherens junctions . Enable the cells in the tissue to use their actin cytoskeletons in a co- ordinated way

8. DESMOSOMES Desmosomes are a type of anchoring junction in animal tissues that connect adjacent cells. Anchoring junctions are button-like spots found all around cells that bind adjacent cells together. Desmosomes have intermediate filaments in the cells underneath that help anchor the junction, while the other type of anchoring junction, an adherens junction, is anchored by microfilaments

9. TIGHT JUNCTIONS Tight junctions are areas where the membranes of two adjacent cells join together to form a barrier. The cell membranes are connected by strands of trans-membrane proteins such as claudins and occludins . Tight junctions bind cells together, prevent molecules from passing in between the cells, and also help to maintain the polarity of cells. They are only found in vertebrates, animals with a backbone and skeleton; invertebrates have septate junctions instead.

10. GAP JUNCTIONS Gap junctions are a type of cell  junction in which adjacent cells are connected through protein channels. These channels connect the  cytoplasm  of each cell and allow molecules, ions, and electrical signals to pass between them . Gap junctions are important during embryonic development, a time when neighboring cells must communicate with each other in order for them to develop in the right place at the right time. If gap junctions are blocked, embryos cannot develop normally. Gap junctions make cells chemically or electrically coupled. This means that the cells are linked together and can transfer molecules to each other for use in reactions. Electrical coupling occurs in the heart, where cells receive the signal to contract the heart muscle at the same time through gap junctions. It also occurs in neurons, which can be connected to each other by electrical synapses in addition to the well-known chemical synapses that neurotransmitters are released from. When a cell starts to die from disease or injury, it sends out signals through its gap junctions. These signals can cause nearby cells to die even if they are not diseased or injured. This is called the “ bystander effect ”, since the nearby cells are innocent bystanders that become victims. However, sometimes groups of adjacent cells need to die during development, so gap junctions facilitate this process. In addition, cells can also send therapeutic compounds to each other through gap junctions, and gap junctions are being researched as a method of therapeutic drug delivery.

11. GAP JUNCTIONS CONTD…… In vertebrate cells, gap junctions are made up of connexin proteins . The cells of invertebrates have gap junctions that are composed of innexin proteins, which are not related to connexin proteins but perform a similar function . Groups of six connexins form a connexon , and two connexons are put together to form a channel that molecules can pass through. Other channels in gap junctions are made up of pannexin proteins. Relatively less is known about pannexins ; they were originally thought only to form channels within a cell, not between cells.

12. INTEGRINS I ntegrins are proteins that function mechanically, by attaching the cell cytoskeleton to the extracellular matrix (ECM), and biochemically, by sensing whether adhesion has occurred. The integrin family of proteins consists of alpha and beta subtypes, which form transmembrane hetero- dimers . Integrins function as adhesion receptors for extracellular ligands and transduce biochemical signals into the cell, through downstream effector proteins . Remarkably, they function bidirectionally , meaning they can transmit information both outside-in and inside-out

13. EXTRA-CELLULAR MATRIX Most animal cells release materials into the extracellular space, creating a complex meshwork of proteins and carbohydrates called the  extracellular matrix  ( ECM ). A major component of the extracellular matrix is the protein  collagen . Collagen proteins are modified with carbohydrates, and once they're released from the cell, they assemble into long fibers called collagen fibrils. In the extracellular matrix, collagen fibers are interwoven with a class of carbohydrate-bearing  proteo-glycans , which may be attached to a long polysaccharide backbone.